This project is organized around the study of the neuroendocrine responses of formerly isolated mice living in population cages in which they experience intense mutual psychosocial stimulation. Sustained high blood pressure and pathophysiological deterioration involving arteriosclerosis, myocardial fibrosis, and chronic nephritis develop in these colonies, and we consider them models of essential hypertension. The main objective is to study the accelerating effect of caffeine-containing beverages on the course of this slowly developing cardiovascular disease process. Quantitative measures of behavior in the colonies are needed, and our technique of magnetic monitoring is being evaluated for error and possible artifact and refined. Observations continue of the function of the newly rediscovered autonomic innervation of the adrenal cortex in determining the corticosterone response to situations arousing fighting, as opposed to avoidance activity. There is now good evidence that both tea and coffee of standard brew accelerate renal damage when animals are competing, but not when they are pacific. The data suggests that the caffeine content is critical and that levels of psychosocial stimulation must also be defined. We are attempting to work out some measure of dose response for the effects of caffeine plus psychosocial stimulation. Behavior, hormone levels, and pathophysiology will be followed as the colonies age. We will continue to pursue the hypothesis that there is a sympathetic adrenal medullary bias in colonies of young fighting animals as opposed to pituitary-adrenal-cortical stimulation in those that are aging and avoiding conflict. BIBLIOGRAPHIC REFERENCES: Henry, James, P. Understanding the Early Pathophysiology of Essential Hypertension. Geriatrics 30 (l): 59-72 (January), l976. Ely, Daniel L., Ernest G. Greene, and James P. Henry: Minicomputer Monitored Social Behavior of Mice with Hippocampus Lesions. Behavioral Biology l6 (1):1-29 (January), l976.